Mouse leukemia cells bearing TL surface antigens escape from destruction in mice immunized against those antigens, but the same cells are effectively killed when other antigens (e.g., H-2) serve as targets. Correlating with escape is the tendency for TL plus tumor cells to acquire resistance to TL antibody-\and guinea pig complement-mediated lysis following exposure to TL alloantiserum (antigen modulation, or evasion). Evasion also affects some mouse lymphomas expressing murine leukemia virus major envelope glycoprotein, MuLV gp70. Evasion-positive tumors grow in all syngeneic mice immunized against gp70 by passive immunization with xenoantisera, whereas evasion-negative tumors are rejected by some immunized mice and growth is markely suppressed in others. Evasion-positive and -negative variants of FLC745 and RBL-5 lymphomas are being studied to establish the relationship between antigen evasion and tumor escape. Xenoantisera, mouse antisera and monoclonal antibodies to gp70 and other MuLV components expressed on the cell surface will be utilized, and evasion of cytolysis will be measured in a radiochromium release assay. Antigen lateral mobility, antibody-induced antigen aggregation and steric hindrance of complement binding (guinea pig Clq) are apparently responsible for evasion. Factors not directly related to antigen evasion include: (1)\quantitative representation of target antigens before and during antibody sensitization and quantitative aspects of antibody binding; (2)\the manner of antigen presentation at the cell surface, molecular associations, molecular and ultrastructural organization; and (3)\differences in detected antigen specificities. Defense mechanisms involved in rejection of evasion-negative tumors are being examined, and a fully homologous (mouse antisera and complement) antigen evasion assay is being developed.